The University of Washington (UW) Chronic Fatigue Syndrome Cooperative Research Center (CFS CRC) continues an integrated, multi- faceted research program that capitalizes on several large, well-organized data bases already collected and addresses a number of practical and theoretical issue sin the epidemiology, clinical assessment, etiology and pathophysiology of CFS. The 4 Projects reflect our central theme: the examination of genetic and environmental influences on the biological and psychosocial characteristics of CFS. Our research has sought to operationalize an explanatory model of CFS that emphasizes 5 dynamic elements and their interaction with respect to risk, onset and course. These elements referred to as the "5 Ps" include predisposing, precipitating, predictive, perpetuating and perceptual factors. CFS may occur in a vulnerable individual in whom genetic, environmental or other predisposing factors are present. Subsequently, an acute or chronic stressor precipitates illness. During a transition period, predictors of chronically become apparent. Symptoms lead to disability, which is both due to, and results in, psychological distress, social dysfunction and other factors that perpetuate illness. Lastly, the individual's perceptual style serves as a context in which the other 4 factors affect the illness. With this model in mind, the objectives of the next period of support for this CFS CRC are to: 1) further characterize CFS using monozygotic twins discordant for CFS and to expose subjects to biological and behavior "stressors" in a theoretically guided fashion to investigate predisposition and perceptions in CFS; 2) confirm the clinical and laboratory abnormalities seen in our current intensive study of CFS-discordant monozygotic twins in sleep, neuropsychological function, immunological parameters and exercise capacity by re-examining these twins and adding a new comparison group of health twin pairs; 3) to define the relative contributions of predispositional genetic or common environmental effects using biometrical genetic analyses of population-based twin study; 4) compare the children of CFS cases and the children of healthy controls to determine the impact of parental illness and to examine if predispositional and perceptual styles are vertically transmitted across generation; 5) explore the role of perpetuators and perceptions in the context of an observational study of interactions between CFS patients and their partners; and 6) to follow-up a well-characterized patient sample to further describe the natural history, prognosis and predictors of outcome of CFS.